白藜芦醇对慢性阻塞性肺疾病大鼠 p38丝裂原活化蛋白激酶/核因子-κB信号通路的影响

Effect of resveratrol on p38 mitogen-activated protein kinase/NF-κB signaling pathway in rats with chronic obstructive pulmonary disease

目的:探讨白藜芦醇对慢性阻塞性肺疾病(COPD)大鼠p38丝裂原活化蛋白激酶(MAPK)/核因子-κB(NF-κB)信号通路的影响。方法:将50只SD大鼠随机分为正常组,模型组,白藜芦醇低剂量组、白藜芦醇中剂量组、白藜芦醇高剂量组,每组10只。模型组及白藜芦醇组采用烟熏联合脂多糖气道内注射法复制COPD大鼠模型,模型构建成功后,白藜芦醇低、中、高剂量组大鼠分别灌胃给予5、15、45 mg/(kg·d)白藜芦醇,正常组及模型组给予等量0.9%氯化钠溶液,连续28 d。HE染色观察肺组织病理形态,分光光度法检测丙二醛(MDA)及超氧化物歧化酶(SOD)水平,酶联免疫吸附(ELISA)法检测肺组织中肿瘤坏死因子-α(TNF-α),白介素-8(IL-8),基质金属蛋白酶-9(MMP-9)及基质金属蛋白酶抑制剂-1(TIMP-1)含量,Western blot检测p38MAPK/NF-κB信号通路相关蛋白表达情况。结果:与模型组比较,白藜芦醇低、中、高剂量组肺泡结构较为完整,有少量炎性细胞浸润,TNF-α、IL-8、MDA、MMP-9含量降低、p38 MAPK、核因子κB抑制因子α(IκB α)及NF-κB p65表达下调,SOD活性及TIMP-1含量升高。结论:白藜芦醇能够缓解COPD大鼠肺损伤,可能与抑制p38 MAPK/NF-κB信号通路有关。

Objective:To explore the effect of resveratrol on p38 mitogen activated protein kinase(MAPK)/nuclear factor-κB(NF-κB)signaling pathway in rats with chronic obstructive pulmonary disease(COPD).Methods:Fifty SD rats were randomly divide into normal group,model group,resveratrol low-,medium-,and high-dose groups,with 10 rats in each group.Model and resveratrol group was established by smoking combined with lipopolysaccharide airway injection method.After successful model construction,resveratrol low-,medium-,and high-dose groups were given 5,15,45 mg/(kg·d)resveratrol by gavage,respectively.The normal group and model group were given equal amounts of 0.9%sodium chloride solution,for 28 consecutive days.The pathological morphology of lung tissue was detected by HE staining.The levels of malondialdehyde(MDA)and superoxide dismutase(SOD)were detected by spectrophotometry.The levels of tumor necrosis factor in lung tissue-α(TNF-α),interleukin-8(IL-8),matrix metalloproteinase-9(MMP-9)andtissue inhibitor of metalloproteinases-1(TIMP-1)were detected by ELISA.The expressions of p38MAPK/NF-κB signal pathway related protein were detected by Western blot.Results:Compared with the model group,in the resveratrol low-,medium-,and high-dose groups,the alveolar structure was relatively complete,with a small amount of inflammatory factor infiltration,the levels of TNF-α,IL-8,MDA,MMP-9,the expressions of p38 MAPK,inhibitor of NF-κB(IκBα)and NF-κB p65 were decreased,the activity of SOD and level of TIMP-1 were increased.Conclusion:Resveratrol can alleviate lung damage in COPD rats,which may be related to the inhibition of p38MAPK/NF-κB signaling pathway.